期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 32, 页码 13020-13025出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1306900110
关键词
cell; gene
资金
- Croucher Foundation
- European Molecular Biology Organization
- Medical Research Council
- Wellcome Trust
- Cancer Research UK
- Cancer Research UK [12386] Funding Source: researchfish
Cohesin's Smc1 and Smc3 subunits form V-shaped heterodimers, the nucleotide binding domains (NBDs) of which bind the C- and N-terminal domains, respectively, of the alpha-kleisin subunit, forming a large tripartite ring within in which sister DNAs are entrapped, and thereby held together (sister chromatid cohesion). During replication, establishment of stable cohesion is dependent on Eco1-mediated acetylation of Smc3's NBD, which is thought to prevent dissociation of alpha-kleisin from Smc3, thereby locking shut a DNA exit gate. How Scc3 and Pds5, regulatory subunits bound to alpha-kleisin, regulate cohesion establishment and maintenance is poorly understood. We show here that by binding to alpha-kleisin adjacent to its Smc3 nucleotide binding N-terminal domain, Pds5 not only promotes cohesin's release from chromatin but also mediates de novo acetylation of Smc3 by Eco1 during S phase and subsequently prevents de-acetylation by the deacetylase Hos1/HDAC8. By first promoting cohesin's release from chromosomes and subsequently creating and guarding the chemical modification responsible for blocking release, Pds5 enables chromosomal cohesin to switch during S phase from a state of high turnover to one capable of tenaciously holding sister chromatids together for extended periods of time, a duality that has hitherto complicated analysis of this versatile cohesin subunit.
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